Difference Between HER2-positive and HER2-Negative Breast Cancer?
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HER2-positive breast cancer are known for there high levels in protein human epidermal growth factor receptor 2. This kind of cancer are known to grow and spreads more rapidly than that of the HER2-negative breast cancer, but they are not nearly as common.
HER2 proteins in breast cancer
If you have a loved one or a friend who has received a breast cancer diagnosis, you would have probably heard the term called HER2. You may be wondering what it means to have HER2-negative or HER2-positive breast cancer.
HER2 stands for human epidermal growth factor receptor 2. The HER2 protein was discovered in the 1980s.
HER2 proteins are found on the surface of breast cells. They’re involved in normal cell growth but can become overexpressed. This means that a person’s levels of the protein are higher than usual.
In the 1980s, researchers determined that too many HER2 proteins could cause cancer to grow and spread more quickly. This discovery led to research on how to slow or alter the growth of HER2-positive breast cancer cells.
What HER2-negative means
If breast cancer cells do not have abnormal levels of HER2 proteins, the breast cancer is considered HER2-negative.
Even if your cancer is HER2-negative, it may still be estrogen-positive or progesterone-positive. Whether or not it’s hormone-positive also affects your treatment options.
In the United States, HER2-negative cases accounted for 78% of new female breast cancer cases between 2015 and 2019, according to the National Cancer Institute (NCI). In 7% of cases, the HER2 status was unknown.
|HER2-negative breast cancer||HER2-positive breast cancer|
|does not have abnormal levels of HER2 proteins||has abnormally high levels of HER2 proteins, causing the cancer to grow and spread more quickly|
|accounted for 78% of new female breast cancer cases in the United States between 2015 and 2019||accounted for 14% of new female breast cancer cases in the United States between 2015 and 2019|
|can be hormone-positive or hormone-negative||can be hormone-positive or hormone-negative|
|less likely to be treated with targeted therapies||primarily treated with the targeted therapy trastuzumab (Herceptin), but may also be treated with one or more other targeted therapies, including pertuzumab (Perjeta)|
|may also be treated with chemotherapy||may also be treated with chemotherapy|
What HER2-positive means
HER2-positive breast cancers have abnormally high levels of HER2 proteins.
This can cause the cells to multiply more quickly. Excessive reproduction can result in a fast-growing breast cancer that’s more likely to spread.
HER2-positive cases accounted for 14% of new female breast cancer cases in the United States between 2015 and 2019.
In the last 3 decades, significant progress has been made regarding treatment options for HER2-positive breast cancer.
HER2-low breast cancer
HER2-low breast cancer is a new classification that’s used to describe cancer where HER2 proteins are present, but there aren’t enough for the cancer to be considered HER2-positive. These cancers have traditionally been classified as HER2-negative.
Around 50% to 60% of breast cancers are actually HER2-low breast cancers, according to the National Cancer Institute (NCI).
Treatment may include the targeted therapy fam-trastuzumab deruxtecan (Enhertu).
Testing for HER2
It’s important for a doctor to test for overexpression of HER2 because the results will determine whether you’ll benefit from certain medications.
Tests that can determine HER2 status include:
- in situ hybridization (ISH) tests, such as the fluorescence in situ hybridization (FISH) test
- immunohistochemistry (IHC) test
For both tests, you’ll provide a tissue sample.
An ISH test is a type of genetic test. During this test, a pathologist examines your DNA to see if you have too many copies of the HER2 gene. In an IHC test, a pathologist actually counts the number of HER2 proteins on the breast cancer cells.
The Food and Drug Administration (FDA) has approved several types of ISH and IHC tests.
ISH tests are not as widely available as IHC tests, but they’re more accurate.
How HER2 affects staging
As of 2018, the breast cancer staging system that the American Joint Committee on Cancer developed now incorporates HER2 status.
Your HER2 status can help determine how aggressive your cancer is. Your doctor will use this information to evaluate your treatment options.
Staging is complex and must take various other factors into account as well, such as:
- the size of the tumors
- the cancer’s hormone status
- whether the cancer has spread to nearby lymph nodes
- whether the cancer has spread beyond the breast
- whether the cancer cells look unusual
For example, these two cancers are both classified as stage 1B:
|HER2-negative breast cancer (stage 1B)||HER2-positive breast cancer (stage 1B)|
|tumors between 2 and 5 centimeters (cm)||tumors between 2 and 5 cm|
|hormone-positive||estrogen-positive and progesterone-positive|
|has not spread to the lymph nodes or away from the breast||has spread to 1 of 3 axillary (armpit) lymph nodes|
Speak with your doctor if you’d like to learn more about your cancer stage.
How HER2 status affects treatment
For more than 30 years, researchers have been studying HER2-positive breast cancer and ways to treat it.
Targeted therapies have now changed the outlook for people with stage 1, 2, and 3 breast cancers from poor to good.
While targeted therapies are part of the standard treatment for HER2-positive breast cancer, they’re used less often in HER2-negative breast cancer.
In general, your breast cancer treatment regimen will depend on your cancer’s:
- HER2 status
- hormone receptor status
For HER2-positive or HER2-negative breast cancers that are estrogen-positive or progesterone-positive, treatment with hormone therapy may also be recommended.
Some people may also receive chemotherapy, depending on their cancer stage.
Other factors that may affect your breast cancer treatment regimen include whether:
- you’ve already received hormone therapy or chemotherapy
- you’ve gone through menopause
- you have gene mutations other than HER2
Treatments for HER2-negative breast cancer
Medications that may be used to treat HER2-negative breast cancers that are hormone-negative include:
- pembrolizumab (Keytruda)
- sacituzumab govitecan (Trodelvy)
- talazoparib (Talzenna)
Medications that may be used to treat HER2-negative breast cancers that are hormone-positive include:
- abemaciclib (Verzenio)
- alpelisib (Piqray)
- everolimus (Afinitor)
- olaparib (Lynparza)
- palbociclib (Ibrance)
- ribociclib (Kisqali)
Most of the medications in the previous list are taken in combination with some form of hormone treatment.
Treatments for HER2-positive breast cancer
Trastuzumab (Herceptin), when used in tandem with chemotherapy, has improved the outlook of those with HER2-positive breast cancer. This targeted drug is often the primary treatment for the condition.
Trastuzumab (Herceptin) is a biologic therapy that’s administered intravenously.
A 2018 literature review showed that the use of trastuzumab with chemotherapy slowed the growth of HER2-positive breast cancer better than chemotherapy alone. For some, this combination has resulted in long lasting periods of remission.
Curative treatment with this medication lasts for up to 52 weeks. If you have metastatic or recurrent cancer, you may take it for much longer. Cardiac monitoring will continue for at least 2 years after treatment ends, due to the risk of side effects.
Other treatments for HER2-positive breast cancer include but are not limited to these targeted therapies:
- Herceptin biosimilars: Biosimilars are not exact copies of biologic drugs, but they’re reverse-engineered to produce similar effects. The FDA has approved five Herceptin biosimilars, including trastuzumab-dkst (Ogivri) and trastuzumab-qyyp (Trazimera).
- Trastuzumab/hyaluronidase-oysk (Herceptin Hylecta): The FDA approved Herceptin Hylecta in 2019. Herceptin Hylecta is an injectable medication. As a result, it can be administered more quickly than Herceptin. Cardiac monitoring is also required.
- Pertuzumab (Perjeta): In some cases, pertuzumab (Perjeta) may be used in conjunction with Herceptin. This may be recommended for HER2-positive breast cancers at a higher risk of recurrence, like stage 2 and above, or for cancers that have spread to the lymph nodes.
- Neratinib (Nerlynx): Neratinib (Nerlynx) may be recommended after treatment with Herceptin in cases that have a higher risk of recurrence.
- Margetuximab-cmkb (Margenza): This is one of the newest HER2 medications. It’s used to treat more advanced or metastatic breast cancer in people who have received at least two previous HER2 treatments.
- Fam-trastuzumab deruxtecan (Enhertu): This versatile medication is used as a second- or third-line treatment for non-small cell lung cancer, advanced stomach cancer, and some cases of HER2-positive breast cancer. This includes cases where the breast cancer cannot be removed with surgery or it’s metastatic. In August 2022, the FDA also approved its use in some cases of HER2-low metastatic breast cancer.
If you’ve received a diagnosis of invasive breast cancer, a doctor will test your cancer to determine its HER2 status. The test results will help inform which treatment options are best for your cancer.
New developments in the treatment of HER2-positive breast cancer have improved the outlook for people with this fast-growing type of cancer. Research is underway for new treatments, and survival rates for people with breast cancer are improving all the time.
If you receive a diagnosis of HER2-positive breast cancer, do not hesitate to talk openly with a doctor about your cancer and ask any questions that you may have.
Frequently Asked Questions
What does it mean if you are HER2-negative?
Is it better to be HER2-positive or triple negative?
Is HER2-positive a good thing?
Do you need chemo with HER2-negative?
Can HER2-negative Be Cured?
What is the best treatment for HER2-negative?
Do all HER2-positive cancers need chemo?
Should HER2-positive have mastectomy?
Does HER2-positive need chemo?
Does HER2-positive come back?
Can HER2 change from negative to positive?
What triggers HER2-positive?
Does HER2-negative spread to brain?
What percentage of breast cancers are HER2-negative?
Do all breast cancers have HER2?
Does HER2-positive mean metastatic?
Is it better to be estrogen positive or negative?
What are the chances of HER2 coming back?
Which breast cancers require chemotherapy?
What chemo is used for HER2-positive?
What stage is invasive ductal carcinoma?
How can I lower my HER2 protein naturally?
How many rounds of chemo is normal?
Is HER2 a good prognosis?
Does HER2-positive run in families?